TETA analogue containing one methylenephosphonate pendant arm: lanthanide complexes and biological evaluation of its Sm-153 and Ho-166 complexes

The thermodynamic stability constants of complexes of 1,4,8,11-tetraazacyclotetradecane-1,4,8-triacetic-11-methylphosphonic acid (H(5)te3a1p) with La3+, Sm3+, Gd3+, Ho3+ and Lu3+ metal ions were determined by potentiometric titrations at 298.2 K and with ionic strength 0.10 M in N(CH3)(4)NO3. The complexes are formed relatively fast and the stability constants exhibited are good although lower than those found for the related ligands H(4)teta and H(8)tetp. At physiological pH the completely deprotonated complex species predominate, unlike what happens with the other mentioned ligands. The Sm-153 and Ho-166 complexes, (153)sm/Ho-166-te3a1p, were synthesised quantitatively at pH 9 and 70 degrees C, and have shown good in vitro stability in human serum and physiological solutions except phosphate buffer (pH 7.4). The in vivo behaviour indicated that both complexes have a similar biological pattern, showing a slow tissue clearance, slow rate of total radioactivity excretion and some in vivo instability, although with some differences in their extend. These results indicate that the replacement of one acetate pendant arm of H4teta by a methylphosphonate one does not provide promising chelators to stabilize radio-lanthanides for in vivo application.